It is known that 2-(2-fluorobiphenyl-4-yl)propanoic acid or pharmaceutically acceptable salts thereof which have anti-inflammatory action, analgesic action and so forth find extensive use as drugs. Processes so far reported for the production of 2-(2-fluorobiphenyl-4-yl)propanoic acid include, for example, a method of obtaining the same using 2-(2-fluorobiphenyl-4-yl)magnesium bromide and a metal salt of 2-bromopropionic acid (Patent Literature 1) and a method of obtaining the same from an ester intermediate prepared using 2-(2-fluorobiphenyl-4-yl)magnesium bromide, a 2-bromopropionic acid ester, and a nickel catalyst (Patent Literature 2). However, each of these methods ends up with synthesis of a racemate and to obtain optically active 2-(2-fluorobiphenyl-4-yl)propanoic acid, it is further required to perform subsequent optical resolution. A method so far reported for optical resolution is by forming a salt with, for example, an optically active amine so that a salt of one of the two optical isomers is allowed to crystallize preferentially but to obtain 2-(2-fluorobiphenyl-4-yl)propanoic acid of high optical purity, more than one recrystallization step is essential, with the recovery being as low as about 60% (Patent Literature 3). In addition, a method so far reported for asymmetric synthesis is by asymmetric hydrogenation of 2-(2-fluorobiphenyl-4-yl)acrylic acid (Non-Patent Literature 1) but this is not a practical approach because not only does it involve a lot of steps but at the same time a toxic rhodium catalyst is used in the final step.
As techniques for constructing a carbon-carbon bond stereospecifically at α-position of carbonyl, Non-Patent Literature 2 reports asymmetric Kumada reaction that uses a nickel catalyst and an optically active bisoxazoline ligand on the substrate α-haloketone whereas Non-Patent Literature 3 and Non-Patent Literature 4 report asymmetric Negishi reaction in which α-haloamide and α-haloketone are respectively used as a substrate. However, asymmetric Kumada reaction requires low reaction temperatures ranging from −60 to −40° C.; in addition, neither asymmetric Kumada nor Negishi reaction is suitable for use in industrial-scale production because both reactions use 6.5 to 13% of an optically active bisoxazoline ligand as obtained by multi-stage synthesis, and there are no reports made on the synthesis of profens, nor on the synthesis using as a substrate, α-haloesters that can be easily derived to profens. As regards the construction of profen structures, asymmetric Kumada reaction that uses a cobalt catalyst and an optically active bisoxazoline ligand has been reported in Patent Literature 4, Patent Literature 5 and Non-Patent Literature 5, and asymmetric Kumada reaction using an iron catalyst and an optically active bisoxazoline ligand has been reported in Non-Patent Literature 6. However, none of these approaches are suitable for use in industrial-scale production because asymmetric Kumada reaction using a cobalt catalyst involves the very low reaction temperature condition of −80° C. and, further in addition, each of the reactions mentioned above uses 6 to 12% of the optically active bisoxazoline ligand.
Hence, it has been desired to develop a process suitable for industrial-scale production of optically active 2-(2-fluorobiphenyl-4-yl)propanoic acid.